Dissociating the Psychoactive Effects of Distinct Cannabis Compounds in the Mesocorticolimbic Circuitry
Master of Science
Dr. Steven Laviolette
The discovery of the endocannabinoid system propelled understanding of the mechanisms of action of cannabinoid compounds. While marijuana is the most widely used illicit substance in the world, the neuropsychopharmacological mechanisms that underlie the diffuse effects of cannabis in the brain remain poorly understood. This is because marijuana smoke represents a complex mixture of chemical components, possessing dissociable psychoactive properties. Clinical evidence suggests a functional dissociation between the two main pharmacological components of cannabis, Δ9- tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). Using a combination of cortical microinfusions during two emotional learning paradigms, and single-unit in vivo electrophysiological recording, we investigated the effects of phytocannabinoid compounds in emotional regulation neural circuits, specifically the nucleus accumbens shell. We report the first demonstration of hedonic properties of CBD; an effect mediated by 5-HT1A receptors, and decreased VTA dopaminergic activity. In olfactory fear conditioning, Δ9-THC potentiates and CBD attenuates emotionally salient stimuli similar to synthetic cannabinoids.
Zunder, Jordan S., "Dissociating the Psychoactive Effects of Distinct Cannabis Compounds in the Mesocorticolimbic Circuitry" (2014). Electronic Thesis and Dissertation Repository. 2225.